T. Moriguchi et al., A NOVEL KINASE CASCADE MEDIATED BY MITOGEN-ACTIVATED PROTEIN-KINASE KINASE-6 AND MKK3, The Journal of biological chemistry, 271(23), 1996, pp. 13675-13679
A cDNA encoding a novel member of the mitogen-activated protein kinase
kinase (MAPKK) family, MAPKK6, was isolated and found to encode a pro
tein of 334 amino acids, with a calculated molecular mass of 37 kDa th
at is 79% identical to MKK3. MAPKK6 was shown to phosphorylate and spe
cifically activate the p38/MPK2 subgroup of the mitogen-activated prot
ein kinase superfamily and could be demonstrated to be phosphorylated
and activated in vitro by TAK1, a recently identified MAPKK kinase. MK
K3 was also shown to be a good substrate for TAK1 in vitro. Furthermor
e, when co-expressed with TAK1 in cells in culture, both MAPKK6 and MK
K3 were strongly activated. In addition, co-expression of TAK1 and p38
/MPK2 in cells resulted in activation of p38/MPK2. These results indic
ate the existence of a novel kinase cascade consisting of TAK1, MAPKK6
/MKK3, and p38/MPK2.